The project, which is part of the National Cancer Institute's Innovative Molecular Analysis Technologies program, will build on previous work by Brock's team, examining the role of intratumor heterogeneity in treatment.
The National Cancer Institute (NCI) has awarded Amy Brock, an assistant professor in the Department of Biomedical Engineering, and her team with a three-year grant to develop a novel cell barcoding platform for the monitoring and isolation of specific cell lineages within large, highly heterogeneous populations.
This project will build on previous work by Brock’s team, examining the role of intratumor heterogeneity in treatment. Tumors consist of 100 million to 1 trillion cells that vary at the genetic and epigenetic (gene expression) level. Individual cells respond differently to drug treatments. It is crucial to understand how these heterogeneous populations change over time, to better match treatments to patient tumors and to understand and avoid the emergence of chemotherapy-resistant cell populations.
Current approaches use DNA barcodes, unique random sequence tags, as heritable markers within cell populations. These tags can be quantified by next-generation DNA sequencing to track the dynamics of cell lineages. However, this approach is limited in that specific lineages of interest cannot be identified and isolated from the bulk population for downstream analyses.
The Brock Lab is developing a synthetic biology platform to control gene expression in individual lineages of interest. Activation of a lineage-specific reporter enables purification of one or more selected lineages (for example, a subpopulation with high resistance to a first-line chemotherapeutic) for further study. The NCI funds will allow the Brock team to further test and refine this platform in normal and cancerous cells under various evolutionary pressures and chemotherapeutic treatments.
The project will be part of the Innovative Molecular Analysis Technologies (IMAT) program at the NCI. The IMAT initiative identifies and supports the development of entirely novel next-generation technologies with the potential to transform cancer research and treatment.
